Hepatitis B viruses produce acute and chronic hepatitis and predispose to hepatocellular carcinoma. These viruses display both species specificity and hepatotropism, but the molecular bases of these properties are poorly understood. Little is known about how these viruses gain entrance into their host cells, so the contribution of virus-receptor interactions to these properties is uncertain. In this study we propose to isolate and characterize the host cell receptor for the duck hepatitis B virus, an animal model of human HBV. The gene for this molecule will be cloned and sequenced and its normal pathway of expression studied. The tissue and species distribution of the receptor will be determined to define the degree to which the receptor influences host range and tissue tropism. Cell lines and transgenic mice bearing the receptor will be constructed to allow the development of novel systems for examining hepadnaviral replication, persistence and pathogenesis. Information gained from these studies will be applied to the development of strategies for the identification of the human HBV receptor.